6ax7

The crystal structure of a lysyl hydroxylase from Acanthamoeba polyphaga mimivirusThe crystal structure of a lysyl hydroxylase from Acanthamoeba polyphaga mimivirus

Structural highlights 6ax7 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: Activity: Oxidoreductase, with EC number 1.14.11.4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Collagen lysyl hydroxylases (LH1-3) are Fe(2+)- and 2-oxoglutarate (2-OG)-dependent oxygenases that maintain extracellular matrix homeostasis. High LH2 levels cause stable collagen cross-link accumulations that promote fibrosis and cancer progression. However, developing LH antagonists will require structural insights. Here, we report a 2 A crystal structure and X-ray scattering on dimer assemblies for the LH domain of L230 in Acanthamoeba polyphaga mimivirus. Loop residues in the double-stranded beta-helix core generate a tail-to-tail dimer. A stabilizing hydrophobic leucine locks into an aromatic tyrosine-pocket on the opposite subunit. An active site triad coordinates Fe(2+). The two active sites flank a deep surface cleft that suggest dimerization creates a collagen-binding site. Loss of Fe(2+)-binding disrupts the dimer. Dimer disruption and charge reversal in the cleft increase Km and reduce LH activity. Ectopic L230 expression in tumors promotes collagen cross-linking and metastasis. These insights suggest inhibitor targets for fibrosis and cancer. Pro-metastatic collagen lysyl hydroxylase dimer assemblies stabilized by Fe(2+)-binding.,Guo HF, Tsai CL, Terajima M, Tan X, Banerjee P, Miller MD, Liu X, Yu J, Byemerwa J, Alvarado S, Kaoud TS, Dalby KN, Bota-Rabassedas N, Chen Y, Yamauchi M, Tainer JA, Phillips GN Jr., Kurie JM Nat Commun. 2018 Feb 6;9(1):512. doi: 10.1038/s41467-018-02859-z. PMID:29410444 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 6ax7, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image